Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer (DUO-E)

• ClinicalTrials.gov Identifier: NCT04269200
• Recruitment Status: Recruiting
• First Posted: February 13, 2020
• Last Update Posted: March 25, 2021
• Sponsor: AstraZeneca
• Collaborators: The Gynecologic Oncology Group (GOG) Foundation Inc; The European Network for Gynaecological Oncological Trial groups (ENGOT)
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: February 10, 2020
• First Posted Date: February 13, 2020
• Last Update Posted Date: March 25, 2021
• Actual Study Start Date: May 21, 2020
• Estimated Primary Completion Date: September 26, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 12, 2020)

Progression Free Survival (PFS) [ Time Frame: upto to 4 years ]

Defined as time from randomisation to first progression by investigator assessment using modified RECIST 1.1 or death (by any cause in the absence of progression)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 12, 2020)

• Overall Survival (OS) [ Time Frame: Up to 6 years ]
  Defined as the time from randomisation to death due to any cause
• Second Progression (PFS2) [ Time Frame: Up to 6 years ]
  Defined as time from randomisation to the earliest of the progression event subsequent to first subsequent therapy or death
• Objective Response Rate (ORR) [ Time Frame: Up to 4 years ]
  Objective response rate is defined as the proportion of patients with measurable disease at baseline who have confirmed complete response (CR) or partial response (PR) as determined by the Investigator at local site.
• Duration of response (DoR) [ Time Frame: Up to 4 years ]
  Defined as the time from the date of first documented confirmed response (CR/PR) until the first progression or death in the absence of disease progression
• Time to first subsequent therapy (TFST) [ Time Frame: Up to 6 years ]
  Time elapsed from randomisation to first subsequent therapy or death
• Time to second subsequent therapy (TSST) [ Time Frame: Up to 6 years ]
  Time elapsed from randomisation to second subsequent therapy or death
• Time to discontinuation or death (TDT) [ Time Frame: Up to 6 years ]
  Time elapsed from randomisation to study treatment discontinuation or death
• The pharmacokinetics (PK) of durvalumab will be determined after steady state doses [ Time Frame: Up to 4 years ]
  Determination of durvalumab concentration in serum
• Safety and tolerability of drugs by assessment of AEs/SAEs [ Time Frame: Up to 6 years ]
  Graded according to the National Cancer Institute (NCI CTCAE)
• The immunogenicity of durvalumab as determined by concentration of Anti-drug antibodies (ADA) to durvalumab [ Time Frame: Up to 4 years ]
  Determination concentration of Anti-drug antibodies (ADA) to durvalumab in serum

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer
• Official Title: A Randomised, Multicentre, Double-blind, Placebo-controlled, Phase III Study of First-line Carboplatin and Paclitaxel in Combination With Durvalumab, Followed by Maintenance Durvalumab With or Without Olaparib in Patients With Newly Diagnosed Advanced or Recurrent Endometrial Cancer (DUO-E)
• Brief Summary: A study to assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer.

Detailed Description

This Phase III study will assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer.

Target patient population: Adult female patients with histologically confirmed diagnosis of epithelial endometrial carcinoma (excluding sarcomas): newly diagnosed Stage III, newly diagnosed Stage IV, or recurrent endometrial cancer

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

double-blind, placebo-controlled

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Endometrial Neoplasms

Intervention

• Drug: olaparib
  Olaparib tablets
• Biological: durvalumab
  Durvalumab by intravenous infusion
• Drug: durvalumab placebo
  Matching placebo for intravenous infusion
• Drug: olaparib placebo
  Placebo tablets to match olaparib
• Drug: Carboplatin
  Standard of care chemotherapy
• Drug: Paclitaxel
  Standard of care chemotherapy

Study Arms

• Active Comparator: Arm A (control)
  Platinum-based chemotherapy and durvalumab placebo followed by maintenance durvalumab placebo and olaparib placebo (tablets).
  Interventions:

  • Drug: durvalumab placebo
  • Drug: olaparib placebo
  • Drug: Carboplatin
  • Drug: Paclitaxel
• Experimental: Arm B (durvalumab+placebo)
  Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib placebo
  Interventions:

  • Biological: durvalumab
  • Drug: olaparib placebo
  • Drug: Carboplatin
  • Drug: Paclitaxel
• Experimental: Arm C (durvalumab+olaparib)
  Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib.
  Interventions:

  • Drug: olaparib
  • Biological: durvalumab
  • Drug: Carboplatin
  • Drug: Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 12, 2020): 699
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 5, 2025
• Estimated Primary Completion Date: September 26, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥18 years at the time of screening and female.
• Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies, including carcinosarcomas, will be allowed. Sarcomas will not be allowed.

• Patient must have endometrial cancer in one of the following categories:

  1. Newly diagnosed Stage III disease (measurable disease per RECIST 1.1 following surgery or diagnostic biopsy),
  2. Newly diagnosed Stage IV disease (with or without disease following surgery or diagnostic biopsy)
  3. Recurrence of disease where the potential for cure by surgery alone or in combination is poor.
• Naïve to first line systemic anti-cancer treatment. For patients with recurrent disease only, prior chemotherapy is allowed only if it was administered in the adjuvant setting and there is at least 12 months from date of last dose of chemotherapy administered to date of subsequent relapse
• FPPE tumor sample must be available for MMR evaluation.
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment.

Exclusion Criteria:

• History of leptomeningeal carcinomatosis.
• Brain metastases or spinal cord compression.
• Prior treatment with PARP inhibitors.
• Prior immune checkpoint inhibitors or prior treatment with an agent directed to a

stimulatory or co-inhibitor T-cell receptor other than anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Female subjects only

• Ages: 18 Years to 150 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

• Listed Location Countries: Australia, Belgium, Brazil, Canada, China, Colombia, Estonia, Germany, Greece, Hong Kong, Hungary, India, Israel, Japan, Korea, Republic of, Lithuania, Mexico, Poland, Russian Federation, Singapore, United States

Administrative Information

• NCT Number: NCT04269200
• Other Study ID Numbers: D9311C00001; 2019-004112-60 ( EudraCT Number ); GOG-3041 ( Other Identifier: Gynecologic Oncology Group(GOG) Foundation Inc ); ENGOT-EN10 ( Other Identifier: The European Network for Gynaecological Oncological Trial groups ); D9311C00001 ( Other Identifier: AZ DCode )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Responsible Party: AstraZeneca
• Study Sponsor: AstraZeneca

Collaborators

• The Gynecologic Oncology Group (GOG) Foundation Inc
• The European Network for Gynaecological Oncological Trial groups (ENGOT)

Investigators

• Principal Investigator: Shannon N. Westin, MD, MPH, FACOG; The University of Texas MD Anderson Cancer Center

• PRS Account: AstraZeneca
• Verification Date: March 2021